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Medicine and Health Sciences Commons

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Research Methods in Life Sciences

Pharmacy Faculty Articles and Research

Series

2022

Blood–brain barrier

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Full-Text Articles in Medicine and Health Sciences

Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria Oct 2022

Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating …